The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine

Dev Cell. 2014 Dec 22;31(6):690-706. doi: 10.1016/j.devcel.2014.11.002. Epub 2014 Dec 4.

Abstract

The dorsal mesentery (DM) is the major conduit for blood and lymphatic vessels in the gut. The mechanisms underlying their morphogenesis are challenging to study and remain unknown. Here we show that arteriogenesis in the DM begins during gut rotation and proceeds strictly on the left side, dependent on the Pitx2 target gene Cxcl12. Although competent Cxcr4-positive angioblasts are present on the right, they fail to form vessels and progressively emigrate. Surprisingly, gut lymphatics also initiate in the left DM and arise only after-and dependent on-arteriogenesis, implicating arteries as drivers of gut lymphangiogenesis. Our data begin to unravel the origin of two distinct vascular systems and demonstrate how early left-right molecular asymmetries are translated into organ-specific vascular patterns. We propose a dual origin of gut lymphangiogenesis in which prior arterial growth is required to initiate local lymphatics that only subsequently connect to the vascular system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / embryology
  • Body Patterning*
  • Chemokine CXCL12 / metabolism
  • Chickens
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Intestines / embryology*
  • Lymphangiogenesis
  • Lymphatic System / embryology*
  • Lymphatic Vessels / embryology
  • Mesentery
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Oligonucleotide Array Sequence Analysis
  • Quail
  • Receptors, CXCR4 / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Homeodomain Proteins
  • Receptors, CXCR4
  • Transcription Factors
  • Green Fluorescent Proteins
  • homeobox protein PITX2